IMPORTANT ANNOUNCEMENT re Degenerative Myelopathy (DM) - Page 4

I am somewhat dismayed that while there is shouting at the rooftops, it is nothing new. I did all those testings for my dog, and none of them showed any reason for his paralysis, and in the end, the fact that he died is what makes me believe he suffered from DM. We used doxycycline any way. We used prednisone, any way. X-rays seeking disc compression. MRI, showed "activity". Great. What  the researchers are not telling you is what the dog goes through to get those tests done. How it also wears on a GSD. 

1doggie2, again, I am so sorry for you, but if I were you, I would submit a sample to the Missouri University. I also if it wouldn't be too much to ask, is if someone with research experience can explain why DM can not be like ALS. ALS in humans has paralysis that progresses, starting with the limbs and ending in vital organs. At least that is my understanding. 

There is no test to determine if a dog has DM while that dog is alive, unless one believes in the Missouri University test. And that is how I see it.

I will repeat what I said at the outset:
“Whilst other research continues I do agree that we must continue to use the existing test for DM to limit as far as we can the incidence of this condition.
Hopefully everyone will contribute DNA samples to any organisation to further research in this field”  and   “Since it costs nothing to send in samples to further ANY research I think it can only be worthwhile”

Anything is viable in the field of scientific study. What I would not do, despite what has been said by Marjorie, is throw out the existing test.  The worst thing that could happen is that the new research proves to be a blind alley and years down the line the SOD1 gene does turn out to have been a significant factor with or without other contributors, and that this avenue had in the meantime been abandoned.  So, common sense to me at least, says keep the test, use the test – time will tell whether it is effective – we are losing nothing by using it. In the meantime, we keep researching, no one has suggested otherwise.  When I say dogs will be followed through, 1) I do not know whether there is a control group in existence which is being followed by UofM. Or whether puppies resulting from breedings from a control group will be/are being tested. I do agree that it would be a good idea to test progeny to see whether the results are as predicted. That would be easy to do.
My understanding is that research is ongoing through the University of Missouri into DM. The UofM received additional funding for 'mapping additional genes associated with DM', so their research into DM has not ceased.
2) In the long term the owners of dogs given N/N status are certainly going to let us know if they go on to develop DM. It will be public knowledge faster than you can blink.  
Marjorie, I and many others here have been where you are now with your dog and the emotion and anger in your posts is so understandable, but we have been there, and others are there now, so we have no less of a stake in eliminating this dreadful disease. Having been there, nobody, but NOBODY wants ever to be there again, and these days the odds are way too high that we could be.  I don’t doubt that you believe that you are totally correct in saying that there is no value in this test, and no doubt as happens in adversity, you have done an inordinate amount of research into it. But what if you are wrong ?

VETERINARY RESEARCH SCHOLARS PROGRAM 2012

Recent work by veterinarians at MU suggests that canine degenerative myelopathy (DM) may be a new animal model of ALS.

I don’t agree that the GSD can be in a worse position by using the test versus not using the test. No one is discouraging any test or further research by others into the disease. It hasn’t discouraged DOGenes  and I see no reason for it to discourage others. There are always better advances being made in medical science. It does not stand still. Breed clubs can also be highly proactive in driving research projects.   I think anyone with a DM dog should and will willingly submit a DNA sample to any research project, and every single person I know in such a position will do just that. I don't care who solves these problems frankly! I am sure Mary Whitely is a very nice person, and perhaps the reason for the lack of information is perception of the need to protect her research.   I will be one of the first congratulating her if her research is successful. But I think verified identification via a third party is crucial. Would have thought you would have agreed with that Videx! 

And yes, exactly what I was getting at:
It is very worrying how many DOG breeders will look for any and every nit-picking excuse for NOT using a (genuine) DNA Test. *My brackets

*Videx - Define 'genuine' Are you suggesting that UofM, Harvard etc and everyone involved in this research are faking it, botching it, don't know what they are doing...What exactly?

As an aside:
Why is it that some drugs that were designed for one illness work dramatically well for something TOTALLY unrelated, and I mean totally ?

Using your basic premise Marjorie it shouldn't happen because X condition has nothing to do with X condition, never has and never will (one is neurological the other cardiac). In some cases they don't even know why it works. But you know what - it did. I know, I take one of said drugs - off label. 

To me that proves that we should not narrow our thinking to that degree and neither should researchers.



 

Beetree, this is for you. I put this on the board once before, but I will put it on again so you can understand WHY I am taking the position I am taking...

  Fact:   "ALS does not affect a person's ability to see, smell, taste, hear, or recognize
touch."

You can pinch the foot of a dog with DM, and they wont feel it, so how can this
be reconciled with ALS not affecting the ability to recognize touch?   Fact:
" ALS Patients usually maintain control of eye muscles and bladder and bowel
functions, although in the late stages of the disease most patients will need
help getting to and from the bathroom.""

In DM, when the hind end goes, so goes bladder and bowel and bowel control...ask
anyone who has had a DM dog if that dog has been able to maintain bladder and
bowel control. The answer is "NO!" Again, how can this be reconciled with ALS,
when DM dogs lose control of bladder and bowel?

Fact:   " Not all familial ALS cases are due to the SOD1 mutation, therefore other
unidentified genetic causes clearly exist." In fact, only 10-20% of people with familial ALS have a change to the SOD1 gene.. What about the other 80-90%? Only 2% of people with non familial ALS have a change to their SOD1.   FACT:

"The parts of the body affected by early symptoms of ALS depend on which muscles
in the body are damaged first. In some cases, symptoms initially affect one of
the legs, and patients experience awkwardness when walking or running or they
notice that they are tripping or stumbling more often. Some patients first see
the effects of the disease on a hand or arm as they experience difficulty with
simple tasks requiring manual dexterity such as buttoning a shirt, writing, or
turning a key in a lock. Other patients notice speech problems-slurred and nasal
speech; or difficulty chewing or swallowing."

Interesting- DM always progresses from the rear, moving towards the front of the
body. I have never heard of a dog with DM having problems with its front end,
front legs, or chewing and swallowing, before it is already down in the rear.

These are just some of the reasons that make ALS a poor candidate to be called DM in the GSD. I cannot speak for other breeds as I am not familiar with DM in other breeds.

It is hard to believe, to those very familiar with DM, that DM is caused by a change to ONE gene (especially when genetically only 10-20% of people with familial ALS have a change to the SOD1 and only 2% of people with ALS that is non familiar have a chnge to the SOD1.). By taking that position, one is denying the undeniable influence of dark dna or RNA. Dark DNA, for those who do not know, is basically the concept that other genes influence the expression of the main genes that are thought to control genetic disease transmission. This is also the concept of gene “imprinting” where some genes turn on or off and those influence whether other genes function and therefore create consequences. The presence of a single gene change which does not explain who actually gets the disease is only part of the answer. If you don’t find which other genes determine whether the “primary” gene acts, you are missing the answer.

Known mutations in SOD1 account for about 2 percent of all cases of ALS. ... This means only about 2% of all patients with ALS have the SOD1 genetic change. How can a change to the SOD1, in the light of this fact (statistics published by the ALS Association) be the sole cause of DM. It cannot be, if 98% of those diagnosed with ALS have no changes to the SOD1. There is no way to determine, at this time, if changes to the SOD1 are a CASUAL or CAUSUAL relationship, and there is a world of difference between the two! Food for thought, at any rate...DM just doesnt present as ALS, not even when you compare test results between the 2 diseases. They are worlds apart  
There has not been one documented case of DM in the GSD beginning anywhere other than the rear of the dog. Bloodwork, CSF, EMG, MRI and complete Neuro exams give a complete picture of what areas are affected and where the problems lie. That is why proper testing is so important, and eyeball diagnosis are worthless

Routine diagnostics are essential to finding what is causing each disease. There are more things that look like GSDM until you look for the cause. In the end, a thorough necropsy sorts out many of the rest if they cannot be found before death from the disease. Unfortunately not enough people pursue a clinical answer and even fewer perform necropsies at the end to get a pathological diagnosis. Without doing one or both, then most of it is just guessing based upon typical presentations and causes for those presentations. That might have been good enough 40 years ago, but not so much, now. However, profile and signalment, history with clinical signs are how a differential diagnosis can be reached.
As far as diseases being related, or stemming from one problem rather than another, well, I guess all diseases could be swept into a broad category of an immune system failure. However, the etiology of different diseases, the course, the presention and the diagnostic tests for that condition is what makes each disease unique. For example, a condition affecting the upper portion of the spine, possibly mimicking DM, but starting in the cervical area is Wobbler's disease. There are different diseases affecting different portions of the body, and they cant all be lumped into one neat category and it doesn't make them related. That is why there are specific tests for specific diseases. That being said, it is quite possible for any dog, as any human, to have more than one condition at a time. However, the ailment/ailments, be it multiple or singular have their own unique etiology. It is believed that dogs with DM have a greater incidence of perianal fistulas,and vice versa. However, DM is not PAF nor is PAF DM. If the condition affecting the dog had a different etiology than DM, simply put, it would not be DM, but in fact, an additional/another disease which fit the etiology of that particular disease, running concurrently with the DM. DM does not present in the larynx or esophogus-in fact, that is the LAST place it goes, AFTER the dog is already down in the front and the rear. That is not the course and presentation of DM, but rather another disease. Thus the diagnostic tools to help rule in and rule out other diseases. A rose by any other name is still a rose, and in order for a disease to be found, etiology and diagnostics are used for diagnosis. You cant call a chest cold "pneumonia". There has to be a certain set of criteria utilized to make a diagnosis. I suppose one could call it whatever one wants to call it, but that doesn't mean the label is correct. To make a correct diagnosis, again, one must stick to the facts and follow testing procedures for that particular condition. DR Coates has worked under the theory that DM is ALS. Amyotrophic Lateral Sclerosis and related diseases are motor unit diseases where the nerve cells in the body responsible for controlling movement die off leaving the patient weak and with varying degrees of Lower Motor Neuron dysfunction, aka LMN, (loss of reflexes and flaccidity) or Upper Motor Neuron dysfunction (hyperactive reflexes and spasticity). Those causing LMN disease affect the EMG early in the course of the disease. Those causing UMN disease result is selective shrinkage of the motor cortex visible on MRI. Neither of these conditions exist in GSDM.

Immune diseases like MS attack varying parts of the nervous system and one of them, Primary Progressive MS, specifically targets the myelin and axons of the spinal cord leading to UMN signs but without affecting the cell bodies of the neurons (which is what is seen in GSDM on histopathology). The CSF protein is usually normal in ALS, but abnormal in MS. Oligoclonal bands of IgG are common in MS and uncommon in ALS. The recessive forms of ALS are extremely slow in development and do not result in shortened life-span. Even the one motor unit disease known in dogs, Spinal Muscle Atrophy in Brittany Spaniels occurs in young dogs with progressive EMG changes leading to death. That might be more consistent with the “early onset DM reported in the GSD which is not the same disease as GSDM on histopathology.

ALS diseases cause motor problems but not sensory ones. That is they do not cause CP deficits or hypermetria (ataxia in which movements overreach the intended goal.). People do not knuckle and scrap their toes when they walk, they only show weakness. Most of them are painful because of muscle spasms. (Does that sound like GSDM?....NO!)

So, even if there is a genetic change in SOD1 that change must also be explainable based upon the clinical signs. (again, only 2 % of people with ALS have a change to their SOD1 gene!) If not, it may just be a casual relationship not a causal one. GSDM as a pure motor unit disease just does not fit all of the available data.

In case I lost anyone in the above explanation, here it is in lay person's terms:

To simplify- lay person's explanation:

DM Corgis, Boxers, : motor unit disease

DM GSD: Auto-immune disease

DM Corgis, Boxers : Protein is normal in the AO CSF

DM GSD: Protein is normal in the AO CSF but Protein is elevated in the Lumbar CSF

DM Corgis, Boxers: Oligoclonal bands of IgG are uncommon

DM GSDS: Oligoclonal bands of IgG are common in MS

DM Corgis, Boxers: affects cell bodies of neurons

DM GSDS: Does not affect cell bodies of neurons

DM Corgis. Boxers: muscle spasms

DM GSDS: no muscle spasms

DM Corgis, Boxers:EMG is affected early in the disease

DM GSDS: EMG is normal

So how can one scientifically explain away these major differences?  One can simply not ignore these HUGE differences because it is convenient to do so! I can call black "white" but that doesn't make it so. It must be born out by test results. Too much data says that GSDM is an immune mediate chronic neurodegenerative disease associated with demyelination and axonal loss. This is most similar to PPMS rather than ALS.

Dr Coates believes that All dogs have oligoclonal bands and, therefore, they were not important in DM. This is not true and we found that 60% of GSDM patients do have more than one unique clonal band in lumbar CSF which is the definition of oligoclonal band positivity. Finally, she keeps looking for CSF changes in DM in the AO CSF which we have repeatedly shown to be normal. CSF changes in DM occur in the lumbar CSF and if there are changes in the AO sample, there is something other than DM.

Again, the DM of the Corgi and Boxer is not the same as the DM of the GSD. Perhaps in other breeds DM is/is more similar to ALS, but in the DM of the GSD, that is just not the case, born out by the facts and diagnostic tests. Again, I know nothing about DM of other breeds, but I am well educated about the DM of the GSD...I do believe the problem ensues when DM is used across the board as a *catch-all* phrase for all breeds. All breeds get a degeneration of the spine which is both chronic and progressive, but the DM of the GSD is a unique disease. Dr Clemmons program does not work on Corgis and Boxers, it never has, giving rise to even more evidence of a difference between the diseases, both of which are called DM. Therefore, the disease our breed gets should always be referred to as GSDM-German Sheperd Dog Myelopathy, which is just not the same disease, clinically or diagnostically, as the DM of the Corgi/Boxer which was the foundation breeds of the ALS/DM study.

I dont know how to explain it any more clearly. If it is not understandable, then I have failed miserably to educate That failure, however, would not be for a lack of trying...   There has not been even ONE documented case of GSDM starting anywhere in the body other than the rear or even ONE documented case of GSDM producing different diagnostic test results...I would venture to say, however, that if it did, it would be a different disease and not called GSDM. It would not be DM of the GSD because the test results are the test results, and the science behind it and the differences cannot be ignored. The marked differences between the diagnostic results previously mentioned, ie the EMG results, the type of disease, Oligoclonal bands present in one not the other, the muscle spasms vs no muscle spasms, the incontinence in one and complete lack of incontinence in the other, cell body neurons in one being affected, cell bodies in the other not being affected, and so on and so on, point to two different disease processes. 2+2 always has to equal 4. It cant equal 5. (Well, unless I am doing the m-m-m-m-m-m-m-ath... LOL! not my strong suit  
Ok- now my turn to question... How many of you believe the there is only a change to ONE gene that is responsible for ALS, in humans and in other breeds? How many of you believe that RNA or dark dna plays no role in determining who gets DM, or ALS for that matter?

I cannot help but question HOW one test that hasnt been around long enough to follow several generations, can claim to produce DM free lines.. I am worried that unethical breeders will seize upon this, when there is no science to prove this will be the case. There cannot be science in this, as generations havent been followed to prove this is a correct and valid claim. It worries me tremendously that dogs are being thrown out of a gene pool because they carry a change to their SOD1 that only 2% of people with ALS possess.

No one could want DM eliminated more than I do. I have been through the horror of this disease 2 times, now. I have lived, slept, eaten, breathed and enveloped my life in battling this disease. It was a promise I made to Jack Flash, as I held in my arms for the last time. It is a promise I think of, everytime I look at my sweet Missie T, who is now in the advanced stages of DM. It worries me that dogs are being prematurely cut out of a gene pool, making a small gene pool already smaller. Working lines breed to working lines, show lines to show lines, obedience to obedience, am bred to am bred, german to german.. The germans look down on the Am breds and the am breds look down on the german bred dogs. We have already subdivided the breed into so many small sections that I am afraid we are bringing bigger problems upon our breed by eliminating dogs based upon the change to the SOD1, which again is 2%!! Like it or not, there are politics in research, just like there are politics in anything else.

Where is the proof that future generations of clear dogs will never develop DM...How can one make that claim, without having studied generations of clear dogs???? and how can one categorically state that there is only ONE gene responsible for DM, when not enough is known about the triggers for the disease?
 
The DM Flash Test is no longer available due to a lack of research funding People jumping on the Corgi bandwagon pulled the plug on the GSD :( Someone has to be paid to run the test. Dr C will run some for me if I ask, but there just isnt enough dollars to run it in the open way he was running it before. We ran out of funding.
Someone asked me if If the Coates work can be fully generalized that means the dog would never develop DM. However, my answer to that is IF and ONLY IF the relationship between the changes to the SOD1 are causal and not casual... and IF and ONLY IF you buy into DM (*catch all* DM of other breeds) being the same disease as GSDM. I personally do not believe they are the same disease, for if they were, there wouldn't be the tremendous discrepancies between the results of the diagnostic test results. They are not even close- they are at opposite ends of the spectrum. How does one reconcile the science of the results being so drastically different?

The GSDCA gave Dr Coates a huge amount of money to research DM of the GSD. Upon necropsy, only 3 out of 12 dogs were found to have been correctly dx with DM. That is a dismal record- she would have received an "F" if her research was college graded.

I did read her research paper on the SOD1 and only 4 GSDS were used in her original research- the rest were Corgis, Boxers and other breeds which never responded to Dr C's protocol (again pointing to a different disease process). The paper mentioned that one of the methods of subject choice was clinical signs of DM. With her history of only 3 out of 12 being correctly diagnosed in the past, I did not get a warm fuzzy feeling as she clearly showed in her GSDCA research that clinical signs are not a reliable way of diagnosing DM. Despite that record, once again clinical signs was one of the criteria she used for her SOD1 participants

People flocked to purchase Methionine, when she did her GSD research for the GSDCA. However, too much methionine is a bad thing - biochemical measures of damage and good operation that are improved by lowering methionine intake are instead made worse when methionine is supplemented in the diet. Increased Methionine led to oxidative damage to mitochondrial DNA in test subjects conducted elsewhere. More oxidative damage is a bad thing Needless to say, her research clearly showed methionine had no effect upon GSDM. It would have been highly unlikely for Methionine to help DM because in her original abstract, she referred to DM as a muscular disease, which it is NOT!

.   At any rate, I wished to give an explanation for my marked skepticism, just to allay one's impression that my stance is an arbitrary one.   Without a follow up for several generations, how can one claim , with any validity, that a clear DNA SOD1 tested clear dog bred to DNA SOD1 tested clear bitch will produce GERMAN SHEPHERD DM free dogs. IMHO, that is a silly notion, possibly misleading and downright irresponsible without generational follow up studies. If one showed me 10-15 years of progeny of SOD1 tested GERMAN SHEPHERD dogs never developing DM, at that point, I might be convinced. We are not at that point, however. In fact, we are far from it :(

Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group      

--- >  This is simply because "ignorance is bliss" for their Kennel and their Breeding stock. commonly known as "DENIAL"
 

Spot on, Videx! I actually had a breeder who used the SOD1 Test  to have her dogs declared *clear*come to my DM Support Group and advertise DM free puppies!!! OMG! Whay unmitigated gall!  Needless to say, that  made me livid and she was immediately banned from my board and her post removed. How insenstive can human beings be???? I detest people who prey upon others misfortune.  I pray there is such a thing as Karma...

Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group  

--- > Marjorie, I and many others here have been where you are now with your dog and the emotion and anger in your posts is so understandable, but we have been there, and others are there now, so we have no less of a stake in eliminating this dreadful disease. Having been there, nobody, but NOBODY wants ever to be there again, and these days the odds are way too high that we could be.

This is my second go round with DM, not my first.

What makes me angry is that the AKCCHF effectively shuts down all research other than their own because they are a powerful organization flush with money. No one can compete with the resources they have, so they have effectively cut off everyone else's research. They have their favorite researchers who get funded over and over, and they do not go outside their own.

 What I am angry about is the lack of any research funding going to any researchers other than those in the good ole boys club of the AKCCHF. They have their pet researchers, and no one else can get any funding. The AKCCHF throws their weight behind ther chosen *gods* and effectively shut down anyone else's research. They have the power and the money to do so. Thats just plain WRONG!What mak because te be  beca

1doggie2
I am so sorry. I know how you feel all to well. Its just heartwrenching... I will be where you are n ot too long from now, I fear. My heart goes out to you :(

I am sending tons of comforting cyberhugs to you and your beloved fur friend...


 , I am so sorry.... I Sending tons of cyberhugs to you and your beloved fur kid.Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group  

It is clear that many dog owners and breeders need to understand that their is significant financial earnings from many scientific discoveries, and certainly CANINE DNA TESTS. All the organisations researching into genetic diseases are not doing this without looking for a return. They protect their discoveries, even those discovered on the path towards a potential DNA Test, by PATENTS. If an when they discover a GENUINE DNA Test, they can proceed PATENT IT, to PROTECT their sole right to do the DNA Test and once protected, scientifically PUBLISH their DNA Test for other scientists to check and challenge and verify. They can choose to license their DNA Test for other organisations in various countries to do their DNA Test and pay royalties. The problem that can occur is some licensed organisations avoid full accountability of the DNA Tests that they actually do, and therefore pay significantly less royalties to the discoverer and legal owner of the DNA Test.

This is a very competitive industry and many organisations, including Universities, are doing research into numerous Genetic Diseases for dogs. When some organisation makes a discovery, up to and including patented and scientifically published discoveries, other competitor organisations will purposefully sow seeds of doubt about the discovery and check thoroughly published scientific data and remain SILENT when they find the DNA Test is GENUINE. The problem occurs that the seeds of doubt they have sown have a negative effect on many of those people who should use the DNA Test on their breeding stock, and at the same time provide ammunition for the cynical and those breeders who WANT to remain in DENIAL. 

I most certainly hope that a genuine DNA Test for DM will be discovered, patented, scientifically published and offered as soon a possible. I have been led to believe that around 30% of GSD could genetically carry this horrendous disease. Obviously 30% are not affected, but such a percentage of carriers gives me some major concerns. We need to have a DNA TEST to identify them so that breeders may make genuinely informed breeding decisions.

ALL patents and scientic publications for genuine DNA tests are normally available to the public.

Here are some stats for all of you, in relation to the SOD1, comparing the GSD and the Welsh Pembroke Corgi...

Here are the most current numbers for the two breeds.

GSD

Clear             Carrier            At risk           Total
877                 546                 302             1735

PWC Corgi

Clear           Carrier                At risk            Total 
137             546                       736               1419
 
So, of all the PWC tested, there are only 172 clear. I guess that breed is doomed..The PWC Club was one of the breeds sponsoriing the research. In contrast there have been 877 clear GSDS.  There are 301 GSDS at risk and 736 PWC at risk. That is quite a difference, is it not? I am sorry, but this is way too early in research to be claiming the SOD1 is responsible. There is no science behind this as there has been no follow up to even begin to validate their claims. This whole scenario is just way too premature, and I fear for the breeds welfare, not just our breed. No pun intended, but IMHO, they are barking up the wrong tree. When breeders claim they have DM free lines because their dogs tested clear, that says nothing good to me about ethics. That implies that the SOD1 is solid science, and it cannot possibly be solid science for at least another 10-15 years when we can find out what happes with future generations.

Videx is right- this is about publicity, patents and money. Again, how the OFA can push and publicize a test that they do not understand, says it all.

Marjorie
http://www.gsdbbr.org The German Shepherd Dog Breed Betterment Registry
BE PROACTIVE!
http://mzjf.com --> The Degenerative Myelopathy Support Group